Physicochemical studies in our laboratory have shown that homogenates of invasive tumors contrary to those of non-invasive tumors of similar origin, contained specific collagenolytic activity. We propose to isolate, purify, and characterize these collagenolytic systems. Purified enzymes from different tumors will be compared with each other and with normal tissue collagenase by physicochemical and immunological techniques. Non-specific proteases which may be present will also be separated and their action will be studied. The mechanism of production and the immunological properties of these tumor enzymes will be studied in relation to the invasive nature of each tumor as determined by histopathologic manifestation. The possibility of these enzymes being tumor-specific antigens will be examined. In this project it is proposed that tissues from benign or noninvasive tumors which have potential for metastatic change may contain a collagenase precursor, zymogen or an inactive form of enzyme which may become activated during the malignant change by some mechanism to be investigated. A search for immuno-cross reacting enzyme precursors based on the competitive displacement of active enzyme from its antibody is proposed. Shope virus papilloma and its VX-2 carcinoma will be used as an experimental model. The practical application of this project is that hopefully it will provide ideas which may open new possibilities for the future treatment of cancer, at least by limiting invasion and metastases, thus allowing a more successful surgical removal of the primary tumor.